This invention relates to proteins diagnostic for atherosclerosis and other pathological states involving vascular calcification; e.g., arterosclerosis, valve calcification, and prosthesis calcification.
Later stages in the sequelae of atherosclerosis are characterized by the presence of calcified plaques. The amino acid Gamma-carboxyglutamic acid (Gla), which is dependent upon vitamin K for its synthesis and is known to bind calcium, has been studied in connection with such plaques.
Lian et al. (1976) Biochem. Biophys. Res. Comm. 73, 349-355 describes work demonstrating the presence of Gla in the calcified atheromatous plaques in the aortas of patients suffering from advanced atherosclerosis. Uncalcified aorta samples from the same patients contained no Gla.
Fallon et al. (1977) Circulation (Abstract, Supp. III) 56, 167 describes the isolation, from calcified human cardiac valves and aortas, of a polypeptide which contains Gla, and which has a molecular weight of about 2,000. Tissue homogenates were extracted with EDTA and the extracts were desalted, freeze dried, and chromatographed on P-6 resin.
Gla is also found in various circulating proteins not associated with atherosclerosis. Examples are prothrombin, clotting factors VII, IX, and X, Protein C, and Protein S, described in DiScipio et al. (1979) Biochem. 18, 899-904.